4bg1

Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 1-(3-Carboxypropyl)-1-methylpyrrolidin-1-ium chloride

spinqualitylabelsall models 4bg1, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bg1 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.89Å Ligands: 16D, IVL, OGA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BODG_HUMAN Catalyzes the formation of L-carnitine from gamma-butyrobetaine. Publication Abstract from PubMed Gamma butyrobetaine hydroxylase (BBOX) catalyzes the conversion of gamma butyrobetaine (GBB) to L-carnitine, which is involved in the generation of metabolic energy from long chain fatty acids. BBOX inhibitor 3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate (mildronate), which is an approved, clinically used cardioprotective drug, is a relatively poor BBOX inhibitor and requires high daily doses. In this disclosure, we describe the design, synthesis and properties of 51 compounds, which include both GBB and mildronate analogues. We have discovered novel BBOX inhibitors with improved IC50 values; the best examples are in nanomolar range and about two orders of magnitude better when compared to mildronate. For 6 inhibitors, crystal structures in complex with BBOX have been solved to explain their activities and pave way for further inhibitor design. Targeting carnitine biosynthesis: discovery of new inhibitors against gamma-butyrobetaine hydroxylase.,Tars K, Leitans J, Kazaks A, Zelencova D, Liepinsh E, Kuka J, Makrecka M, Lola D, Andrianovs V, Gustina D, Grinberga S, Liepinsh E, Kalvinsh I, Dambrova M, Loza E, Pugovics O J Med Chem. 2014 Feb 26. PMID:24571165 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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